Plastic tablet coating



3,630,273 Patented Apr. 17, 1962 Free 3,030,273 PLASTIC TABLET COATING Roland C. Zagnoli, Highwood, Ill., assignor to Abbott Laboratories, North Chicago, 111., a corporation of Illinois No Drawing. Filed Sept. 2, 1959, Ser. No. 837,586 17 Claims. (Cl. 16782) This invention relates to color stable, plastic coated tablets, and a procedure to manufacture these tablets.

Tablet coating, as such, is a very old art, and up to a few years ago, most tablets for human consumption were coated with sugar solutions and the like. Sugar coating of tablets is a very slow process and usually involves one .or more sub-coatings and up to 100 individual, but extremely thin, sugar coatings. Various dyes that are physiologically acceptable may be incorporated into the sugar solution to give the finished tablet a pleasing appearance.

In recent years, the disadvantages of sugar coating have been overcome by the much more advantageous thin plastic film coating. This plastic coating can be applied in a simple operation taking hours only, where formerly several days of coating were involved, and is therefore much more economical. Other advantages of the recently developed plastic coating of tablets are the low caloric value of this coating, the usability of such tablets for diabetic patients, the elimination of tooth decay from tablet coating sources, and others. Unfortunately, however, these more modern coating compositions are somewhat more diflicult to be colored. The actual difiiculty does not lie with the inability of the plastic coating material to be dyed or pigmented, but with the presence of the incorporated dye or pigment in the very thin film coat of the tablet. The presence of the dye molecules close to or on the surface of the plastic coated tablets exposes them to deteriorative outside factors. The most damaging of these factors is ultra-violet light, to which only very few physiologically acceptable dyes are stable.

To protect the ultra-violet unstable dyes in the plastic coating of the modern tablets, the incorporation of hundreds of protective agents into the plastic coating formulation has been tried with very little success. Selection of such protective agents is hindered by the fact that these agents have to be physiologically acceptable, and they have to be compatible wtih the other ingredients in the tablet coating formulation.

One method of effectively protecting the coloring agent in tablets is by absorbing the ultra-violet portion of natural light by physical means. The color unstable tablets are I stored in containers that filter away the ultra-violet light; 1 e.g., brown containers which have found wide acceptance in the tableting industry. The use of such brown containers, however, has serious disadvantages, i.e., the content of such a container cannot be ascertained by external observation, and the container has to be opened to determine the color, shape, and size of the tablet it contains as well as the size of the remaining stock. A further problem is connected with the inability of these tablets to be exhibited in displays and the like. Obviously, when such color unstable tablets are displayed with disregard to the possible deterioration by ultra-violet light, color fading occurs after a relatively short exposure to sunlight and the tablets become unsightly. This adversely affects consumer acceptance even though the potency of the effective drug remains intact.

Accordingly, it is an object of the present invention to incorporate color into plastic coated tablets in such a fashion that no adverse effect of the ultra-violet light is seen. Another object is the provision of light stable, plastic coated tablets for human consumption. A further object is the provision of a method that applies color, stable to discoloration, to plastic coated tablets. It is a still further object to provide a formulation that is useful for coating medicinal tablets with a color stable plastic material.

These and other objects are accomplished by the provision of a composition containing a water soluble or water dispersible, plastic coating material, one or more physiologically acceptable dyes, and a minor proportion of a complexing agent for these dyes.

It has been found that tannins and albumin severally or jointly are useful agents for this complexing action. Among hundreds of compounds tried for this complexing action, only the above type of materials were found to protect the dye permanently when mixed with a plastic coating material; and without incurring adverse effects on the coating formulation. The term tannin throughout this specification and the claims refers, as generally accepted to such materials as tannic acid (penta-digalloylglycose), Turkish or Chinese tannin, hamameltannin, and similar high molecular weight derivatives from glycose and digallic acid, and mixtures thereof.

The plastic coating formulations are based on water soluble or water dispersible film-forming materials which are partially or completely synthetic. Some of these materials are described in US. 2,881,085 which refers to a combination of a water soluble wax-like material and cellulose esterified partially with lower aliphatic monocarboxylic acids and partially with a polycarboxylic acid. Such esters are described in US. 2,093,462, US. 2,093,464, and US. 2,126,460. An example of such an ester is cellulose acetate phthalate. Other film-forming materials use ful in coating formulations are: the combination of a copolymer of maleic anhydride/ ethylene and partial hydrolysis products thereof described in US. 2,857,365; the combination of water soluble waxes and a cellulose ester of lower aliphatic carboxylic acids, such as cellulose acetate, acrylic polymers and copolymers such as meth acrylate, methylmethacrylate, methylmethacrylate/methacrylic acid, methacrylate/methacrylic acid, acrylate/ methylmethacrylate, methylacrylate/methylmethacrylate, etc.; or vinyl polymers such as polyvinylpyrrolidene/vinyl acetate with a water soluble wax, and similar polymers and copolymers.

The practice of coating tablets and the like with the foregoing plastics involves the steps of dispersing said plastics in a volatile slovent. To this liquid coating composition are added dyes and the complexing agent or agents. The resulting mixture is applied to the solid medicaments rotating in a coating pan. The coating composition is distributed evenly over the surface of the I solid medicament and additional portions of the coating compositions are added to the rotating pan as the solvent from the previous portion evaporates. Each of these coating steps results in a dry, hard film that forms on the medicament. The procedure is repeated until a film of desired thickness is obtained.

The requirement for the film-forming plastic to be Water dispersible comes from the necessity for the plastic covered tablet to disintegrate after ingestion. If the plastic would not disperse, the ingredients inside this plastic coating would never be accessible by the body liquids.

The volatile solvents can be selected from among those in which the foregoing plastics are soluble. This includes lower aliphatic alcohols such as methanol, ethanol, n-propanol, isopropanol and solvents of higher volatility such as acetone, methylene chloride, methylethyl-ketone, ethyl acetate and the like which are miscible with the alcohol solvents. The foregoing solvents of higher volatility can be used in conjunction with the alcohols to accelerate drying of the coating compositions after application to the tablets.

An alternative procedure provides preparing the liquid composition in an anhydrous solvent medium; i.e., organic solvents without water.

Various ingredients may be incorporated and are usually part of the film-forming formulation to attain a more pharmaceutically elegant tablet. The present invention is particularly concerned with stabilization of the coloring agents incorporated in the coating formulation such as non-toxic dyes, lakes, and pigments certified for use in food, drug, and cosmetic industries. The coating composition may also include agents which provide gloss, such as silicone resins, long-chain fatty acids, long-chain metallic soaps, and long-chain alcohols. Opaquing agents may be added to overcome transparency of the film coating. Among them are titanium dioxide, calcium carbonate, dehydrated calcium sulfate, dicalcinm phosphate, and others known in the pharmaceutical art. Suspending agents such as Bentone 18C (alkyl ammonium montmorillonite) and Veegum (5% aqueous suspension of complex colloidal magnesium aluminum silicate) may be used to suspend the opaquing agents and other insoluble materials. Plasticizers are added to render the film coating more flexible, thereby overcoming any brittleness of the film coating. Among the suitable and well known plasticizers are mineral oil, castor oil, polyhydroxy compounds such as polyethylene glycol 200, 300, or 400, propylene glycol, glycerine, and the like. Among the sweetening agents customarily used are vanillin, saccharin, sucaryl (sodium cyclohexylsulfamate), coumarin, heliotropin, etc.

The above complexing agents have a broad range of applicability, but work best when selected by the following simple method of determination. When a complexing agent is to be used for a dye containing one or more sulfonic acid groups in the molecule, albumin is the indicated complexing agent. Where the dye to be stabilized contains one or more basic nitrogen atoms, then tannin is the preferred agent. This is true whether the basic nitrogen is in form of a quaternary ammonium configuration, in form of a primary, secondary or tertiary amine, or as a member of a heterocyclic ring. Where a dye contains both types of mentioned groups, either one or both of the mentioned complexing agents can be used. Where dyes are involved that neither contain sulfonic acid groups nor basic nitrogen configurations, e.g., F.D.&C. Red #3, the pH of a solution of such a dye is measured and, where the pH is above 7, a tannin is used; where the pH is below 7, albumin is used as the complexing agent.

The above outline of a method for selecting the complexing agent operates for the conditions presented, however, in the tableting industry a combination of dyes is usually used; therefore, in most dye mixtures there will be found basic nitrogen atoms as well as sulfonic acid groups. Thus, a combination of albumin and tannin is used in most cases. It may also be said that in cases where tannic acid is used as a complexing agent, a supplementary addition of albumin will not have an adverse effect, even where such an addition is not needed or warranted from the configuration of the dye or dyes. The same, of course, is true for the addition of tannin to formulations Where only albumin is indicated as the active complexing agent. It is for this reason that, where the configuration of the dye or dyes is not known, the addition of a combination of both, tannins and albumin, is always safe and useful in stabilizing the tablet color against ultra-violet light deterioration.

The amount needed is actually very small, and since albumin or tannin are both physiologically acceptable ingredients, even a large excess of such a complexing agent in the composition has no adverse efiect on the consumer after ingestion. Of course, a very minor addition of complexing agent will suffice to stabilize the color in the coating solution or dispersion as well as in the final tablet. These amounts range from about 0.5% wt./vol. to about 3% wt./vol. of total coating dispersion or solution. This, in other words, shows that the additions of 5 to 30 g. of complexing agents to a coating solution of one liter is all that is needed to stabilize the color. One liter of such a coating composition will be suflicient for the coating of about 7,000 medium-size tablets; or one tablet will contain 0.7-4 mg. of complexing agent. Obviously, even smaller amounts will protect the dyes to a certain extent and large excesses are permissible, but the above range indicates the preferred limits.

An operable liquid coating composition according to the v instant disclosure will contain at least a sufiicient amount of plastic to obtain a hard coat on the tablet after drying. The upper limit of plastic in the liquid composition will be determined by the practical consideration of retaining the facility of manipulation with a composition which is not too viscous. A preferred and easily manipulated composition contains about 180-250 grams of plastic in 1 liter of solvent. The amount of dye in said composition is about 0.05-4.0 grams/liter of solvent and the complexing agent which achieves the advantages of the invention is present in about 5-30 grams/liter of the solution. The solvent preferably is a mixture of acetone and alcohol in a ratio of about 2:1, but, of course, other low boiling solvents for the plastic or mixtures thereof may be used with equally good results.

After application of the foregoing liquid compositions to the tablets and after evaporation ofthe solvent or solvents, a hard, dry film is formed. Accordingly, the composition of the film is about 88-97% plastic, about .05-l.5% coloring agent and about 2.5-10.5% of complexing agent.

In preferred final embodiments, -a liquid coating composition will also contain excipients and adjuvants of the type previously enumerated. Thus, in addition to the plastic, coloring agents and complexing agents present, a one liter mixture can contain from 15-25 g. plasticizer, 5-15 g. opaquing agents, 2-5 flavoring agents and 5-10 g. wetting agents. After evaporation of the solvents the composition of the dry film will be altered correspondingly by the presence of these excipients and adjuvants. The

hard plastic film will then comprise about 75-85% plastic, about .02-1% coloring agents, about 2-8% complexing agents, and about 13-16% of excipients and adjuvants.

In order to better understand the present invention, the following examples are given as illustrations. These examples are not intended to limit the invention in any form except as specified in the appended claims.

Fading of tablets coated with colored film-forming materials was tested with an ultra-violet light. This light source is 7% inches long and operates at 150 volts, 5.2 amperes and is placed 10 inches above the tablets. The occurred fading is compared with paper samples that were exposed to sunlight for specified periods (light sensitive paper, lot #1555 from U.S. Bureau of Standards). Calibrating this ultra-violet light source shows that an exposure in this fadometer of 4 /2 hours corresponds with a six months exposure to sunlight. In the test, the tablets are checked after exposing them 22%, 45, 90, 135, and 270 minutes in this fadometer.

EXAMPLE 1 In a small amount of acetone, g. of polyethylene glycol of average molecular weight 6000 are dissolved. This solution is added to 600 cc. of a wt./vol. cellulose acetate phthalate solutionand acetone is added to this mixture with stirring to fill up to 1000 cc. The cellulose acetate phthalate solution contains 'per 1000 cc.: 100 g. of cellulose acetate phthalate, 316 g. of acetone, 32 g. of propylene glycol, 10 g. of a wetting agent and 386 g. of alcohol.

To this mixture is added 0.15 g. of Blue F.D.&C. #2, 2 g. of ethylvanillin, 40 g. of titanium dioxide and 5 g. of white powdered albumin and the mixture is ballmilled overnight. The resulting blue mixture is then applied to a moving bed of tablets or granules by pouring small portions onto the tablets. As the tablets rotate, the coating composition is distributed evenly over the surface thereof and additional portions of the coating mixture are added as the solvent of the previous portions are evaporated, leaving a dry, hard film. This procedure is continued until a film of desired thickness is obtained, without ever interrupting the rotation of the coating drums.

The blue tablets are then dried in the usual manner on trays. They are pleasing in appearance and will disintegrate without delay either in water or in gastric secretions. They do not show any sign of fading after 4 /2 hours exposure in the fadometer. Tablets made in the identical manner but without the complexing agent fade in less than 22 /2 minutes.

The formulations given in the table tabulated below are made up in the same manner as the one described above; however, the albumin used in the above example is replaced in some formulations by tannin or a combination of albumin and tannin, as indicated in the table. The numbers given in the columns for albumin and tannin indicate these respective amounts in g./liter of coating formulation. The fadometer columns give the time elapsed before fading is noticeable and compares tablets not containing any complexing agent (control) with those being made as described in the respective examples. It should, however, be noted that the amounts of the complexing agent is not optimum in all examples and that in several instances longer ultra-violet stability can be achieved by increasing the amount of complexing agent.

Coating Compasmons Dye complexing Fadometer Agent Test Name S04 Basic Albumin Tannin Control Sample groups N in min.

270 270 135 120 90 135 2 90 Yellow 5- 2 2 7 5 90 270 Yellow 6 2 5 22% 270 Violet 1.. 2 3 15 5 22% 270 D. & C. Dyes:

Green 5.. 2 2 5 22% 135 Blue 1.- 3 2 l5 7. 5 270 Blue 4 3 2 5 5 22% 270 Orange #3.-.." 2 '7 22% 135 Orange 4- l 10 22% 270 Red#19- 2 5 22% 90 Red 33.. 1 5 5 22% 90 Red 37.. 2 20 10 45 270 Yellow 10. 2 1 5 5 45 135 Yellow 11 1 6 90 270 Brown 1 1 1 5 222 45 Red Lake 2 20 10 45 270 1 Optimum amount not determined.

EXAMPLE 2 This example shows the procedure to make a large batch of colored coating solution with synthetic film-forming plastic coating materials. To 15 gallons of acetone is added 22.7 kg. of cellulose acetate phthalate. The mixture is agitated and then allowed to soak overnight. A second solution is prepared by mixing 7.05 kg. of propylene glycol, 2.2 kg. of Span (a wetting agent from sorbitol and common fatty acids), and 0.9 kg. of castor oil with a small amount of ethyl alcohol. The two solutions are then combined and mixed by agitation. Additional alcohol is added as necessary.

Into a ballmill of 30 gal. capacity are placed 1893 g. of F.D.&C. Blue #1, 11357 g. of F.D.&C. Yellow #5, 19 kg. of titanium dioxide, 5.7 kg. of albumin, 8.36 kg. of sodium cyclohexylsulfamate, 13.36 oz. of saccharine, 20.04 oz. of heliotropin, 27.38 oz. of coumarin, and 4.04 lbs. of ethylvanillin and ballmilled for 24 hours with sufficient acetone to cover the balls and solid materials. After filling the ballmill with a portion of the above cellulose acetate phthalate solution, the mixture is ballmilled another hour. In a separate container, 56 kg. of polyethylene glycol of average mol. wt. 6000 is melted in 1.9 kg. of cetyl alcohol and half of the above cellulose acetate phthalate solution is added. This mixture is stirred well and combined with that of the ballmill. The ballmill is rinsed with acetone and the rinse is then added to the combined solutions, together with the balance of the cellulose acetate phthalate solution. Af er thorough mixing, 2.9 kg. of tannin is added and sufficient acetone brings the mixture to a total of gallons. Mixing is continued until the tannin is completely in solution which takes about 30 minutes to 1 hour. The coating formulation is then strained and ready for use in tablet coating in the usual manner.

Tablets coated With this formulation have an ultraviolet stability of more than 4 /2 hours in the fadometer. The same formulation without albumin and tannin will fade after less than 1 /2 hours in the fadometer.

The foregoing specific examples demonstrate the effects of the described invention. It will be obvious to those skilled in the art that the amounts of complexing agents cited in these examples are illustrative amounts and do not necessarily prescribe optimum amounts. The results, translated from the fadometer into daylight exposure, demonstrate that the new coating formulation makes the cooled tablets stable to ultra-violet light for periods of 3 to Well above 6 months, whereas prior coating formulations show fading, in most cases, in less than 2 weeks.

As pointed out above, other polymeric materials may replace cellulose acetate/polyethylene glycol, but for convenience, the above examples all refer to the same film coating formulation. This formulation may be a solution or dispersion, the complexing agents having the identical effect on light stability in both. Obviously, other compounds may be mixed in with the above-mentioned ingredients, i.e., sweetening agents, flavoring agents, disintegrators, buffers, etc., as well as other dyes that may be suitable for tablet coloring. As pointed out in the examples, a mixture of dyes and lakes will give equally good results when used in combination with the complexing agents of the present invention.

Others may practice the invention in any of the numerous ways which will be suggested to one skilled in the art upon reading the above procedure. -It is intended that all such practice of the invention will be included hereunder, provided it falls within the scope of the appended claims.

I claim:

' l. A liquid coating composition for applying a thin, color stable plastic film to solid medicaments which comprises a volatile organic solvent containing therein a water dispersible, non-toxic, film forming plastic, a physiologically acceptable coloring agent, and a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at least in part '7 tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

2. A liquid coating composition for applying a thin, color stable plastic film to solid medicaments which comprises a volatile organic solvent containing therein a waterdispersible, non-toxic, film forming plastic, a physiologically acceptable coloring agent, tannin, and albumin.

3. A liquid coating composition for applying a thin, color stable plastic film to solid medicaments which comprises a volatile organic solvent containing therein a water dispersible, non-toxic, film forming plastic, tannin, and a physiologically acceptable coloring agent containing basic nitrogen.

4. A liquid coating composition for applying a thin, color stable plastic film to solid medicaments which comprises a volatile organic solvent containing therein a water dispersible, non-toxic, film forming plastic, albumin, and a physiologically acceptable coloring agent containing sulfonic acid groups.

5. A liquid coating composition for applying a thin, color stable film to solid medicaments which comprises a volatile, organic solvent containing therein about 180- 250 w./v. of a Water dispersible, non-toxic, film forming plastic, about 04-41) W./v. of a physiologically acceptable coloring agent, about 5-30 w./v. of a complexing agent selected from the class consisting of tannin, albumin, and a combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

6. A liquid coating composition for applying a thin, color stable plastic film to solid medicaments which comprises a lower alkanol-acetone mixture containing therein about 180-250 'w./v. of cellulose acetate phthalate, about .044.0 w./v. of a coloring agent, and about 5-30 w./v. of a complexing agent selected from the class consisting of tannin, albumin, and a combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

7. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising a water dispersible, non-toxic plastic, physiologically acceptable coloring agents and a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the furtherprovision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic .nitrogenand sulfonic acid groups.

8. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising a non-toxic, water dispersible, plastic, physiologically acceptable coloring agents, tannin, and albumin.

9. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising a non-toxic, Water dispersible, plastic, tannin, and a physiologically acceptable coloring agent containing basic nitrogen.

10. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising a nontoxic, water dispersible plastic albumin, and a physiologically acceptable coloring agent having sulfonic acid groups.

11. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising a nontoxic, water dispersible plastic, tannin, albumin, and a physiologically acceptable coloring agent having basic nitrogen and sulfonic acid groups.

12. A coated, solid medicament having as the coating material a thin, color stable, plastic film comprising about 75-85 of non-toxic, water dispersible plastic, about .02- l% of a physiologically acceptable coloring agent, about 13-16% of tableting excipients and adjuvants, and about 2-8% of a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the color-ing agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen'and sulfonic acid groups.

13. A coated, solid medicament having as the coating material a'thin, hard, color stable, plastic film comprising about 75-85% of a mixture of cellulose acetate phthalate and polyethylene glycol, about .02-l% of physiologically acceptable coloring agents, about 'l-3-l6% of tableting excipients and adjuvants, and about 2-8% of a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

14. A coated, solid medicament having as the coating material a thin, plastic, color stable film comprising about 88-97% of a non-toxic, water dispersible plastic, about .05-l.5% of a physiologically acceptable coloring agent, and about 2.5-l0.5% of a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

15. The method of coating tablets and the like with a thin, color stable, plastic film which comprises the steps of applying to tablets a liquid composition having a volatile, organic solvent medium which contains therein a nontoxic, water dispersible, film forming plastic, a physiologically acceptable coloring agent, and a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at least in part tannin when the coloring agent contains basic nitrogen, the complexing agent is at least in part albumin when the coloring agent contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin when the coloring agent contains basic nitrogen and sulfonic acid groups.

16. The method of claim 15 wherein the liquid composition contains about -250 w./v. of a non-toxic, water dispersible, film forming plastic, about .04-4.0 w./v. of a physiologically acceptable coloring agent, and about 5-30 w./v. of a complexing agent selected from the class consisting of albumin, tannin, and the combination of tannin and albumin, with the further provision that the complexing agent is at leastjn .part tannin when the 3,030,273 9 10 coloring agent contains basic nitrogen, the complexing References Cited in the file of this patent agent is at least in part albumin when the coloring agent UNITED STATES PATENTS contains sulfonic acid groups, and the complexing agent is a combination of tannin and albumin When the color- Endlcott Aim 1959 ing agent contains basic nitrogen and sulfonic acid groups. 5 OTHER REFERENCES 17. The method of claim 15 wherein the organic sol- Chemistry and Manufacture of Cosmetics, by De varre, Van Nostrand Co., N.Y., 1941, pp. 592, 593.

vent consists of a mixture of a lower alcohol and acetone Synthetic Dyes, Venkataraman, 1952, vol. 11, Academic and contains therein cellulose acetate phthalate, polyethylene glycol, a physiologically acceptable coloring agent, Press NY p 12124215 tannin and albumin. 10

UNITED STATES PATENT OFFICE "CERTIFICATE OF CORRECTION Patent No, 3,030,273 April l7 1962 Roland C. Zagnoli It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent shouldread as corrected below.

Column 1, line 46, for "wtih" read with "-3 column 2, line 52 for "slovent" read solvent --5 column 4 line 50, for "2-5" read 2-5 g. column 5 line 36, for "compares" read compare line 40, for "is" read are -,'3 column 7 line 56 for "agents" read agent line 68, after "dispersible" strike out the comma; line 69 for "agents" read lagent same column T line 72 after "dispersible" strike out the comma; column 8,, line 2 after "plastic" insert a comma.

Signed and sealed this 28th day of August 1962.

(SEAL) Attest:

ZSTON G, JOHNSON DAVID L. LADD testing Officer Commissioner of Patents 

1. A LIQUID COATING COMPOSITION FOR APPLYING A THIN, COLOR STABLE PLASTIC FILM TO SOLID MEDICAMENTS WHICH COMPRISES A VOLATILE ORGANIC SOLVENT CONTAINING THEREIN A WATER DISPERSIBLE, NON-TOXIC, FILM FORMING PLASTIC, A PHYSIOLOGICALLY ACCEPTABLE COLORING AGENT, AND A COMPEXING AGENT SELECTED FROM THE CLASS CONSISTING OF ALBUMIN, TANNIN, AND THE COMBINATION OF TANNIN AND ALBIMIN, WITH THE FURTHER PROVISION THAT THE COMPLEXING AGENT IS AT LEAST IN PART TANNIN WHEN THE COLORING AGENT CONTAINS BASIC NITROGEN, THE COMPLEXING AGENT IS AT LEAST IN PART ALBUMIN WHEN THE COLORING AGENT CONTAINS SULFONIC ACID GROUPS, AND THE COMPLEXING AGENT IS A COMBINATION OF TANNIN AND ALBUMIN WHEN THE COLORING AGENT CONTAINS BASIC NITROGEN AND SULFONIC ACID GROUPS. 